Europe faces many challenges in bringing new medicines to patients in an efficient and timely manner. The reasons for this include the high attrition rates in medicine development, a regulatory environment lagging behind rapidly evolving science, and research and development (R&D) and price/reimbursement models that are no longer financially viable.
Medicines adaptive pathways to patients (MAPPs) refers to a concept that seeks to provide patients with timely access to beneficial medicines, starting from a small group of well-identified patients (e.g. those with no alternative treatments). As evidence accumulates on the benefits and risks of a medicine, access may be extended to other groups of patients. MAPPs relate to a flexible pathway covering the entire life cycle of a medicine, from development, through licensing, to patient access (pricing/reimbursement and healthcare delivery).
By bringing together representatives from key European stakeholder groups – regulatory agencies, health technology assessment (HTA) bodies, pharmaceutical companies, payers, patients and health care professionals – ADAPT-SMART created a platform where the conditions and feasibility of MAPPs implementation within the EU regulatory/legal context could be discussed openly. As a result, the project contributed to an improved understanding among stakeholders of the issues promoting early access of medicinal products to patients.
Embracing the lifespan approach
Thanks to ADAPT-SMART, there is now a wide acceptance among different stakeholders that medicines development should take the lifespan approach. Whereas in the past the prevailing idea was that a drug should be developed for 5 to 10 years, then launched and left out there for patients to use, this project reinforced the idea of continuous evaluation and use. The project came up with recommendations on how the system could be improved at the various decision points in the product lifespan, including before and after licencing. This means that patients who are running out of time could get access to new drugs more quickly, and that evaluation continues even after the product launch.
Other top project outputs include:
- an overview of conditions which need to be met for entering the MAPPs/adaptive pathway;
- a definition of the building blocks for early access, appropriate use and the continuous evaluation of medicines;
- a model for a seamless pathway for early access and continuous evaluations;
- a recognition that there are no legal constraints in implementing an adaptive pathway approach for medicines development, approval and reimbursement;
- a glossary of terms to be used in the debate of adaptive pathways and early access;
- recommendations for potential future IMI research projects which will be important in progressing the implementation of MAPPs.
For the benefit of patients, industry and regulators
Industry has learned the value of interacting with regulators, HTA bodies and patient organisations throughout the drug development process. Different industry partners have also learned that it is possible to work with each other constructively in the pre-competitive space.
Regulators such as the European Medicines Agency also benefitted from their interaction with different stakeholders, especially with HTA bodies and payers. Among other things, having a debate with these downstream decision makers could help them avoid situations where they authorise products which are later rejected for pricing and reimbursement, and never reach patients.
ADAPT-SMART also involved two patient organisations as partners in the project. They helped to set the project goals and get results that are meaningful for patients. Furthermore, the recommendations that the project brought forward acknowledge the important role patients should play in the development, approval, reimbursement and appropriate use of medicines.
The most important results of the project have been published in scientific journals. Additionally, the project published a comprehensive online infographic to help stakeholders to access all the relevant documents. Finally, recommendations and conclusions brought forward by ADAPT-SMART will continue to be debated by different groups of stakeholders, and developed by different groups of researchers, including those involved in future IMI projects.
This project was supported by the Innovative Medicines Initiative, a partnership between the European Union and the European pharmaceutical industry.
Achievements & News
Today’s paradigms of bringing innovation to patients are challenged by new developments, such as a growing patient demand for timely access to promising therapies, and increased fragmentation of patient populations due to better disease stratification. To address these challenges, major adaptations to current paradigms are needed while still staying in the EU legal framework. The ADAPT-SMART project set out to address that gap. ###The project created a multi-stakeholder platform where the conditions and feasibility of medicines adaptive pathway to patients (MAPPs) implementation within the EU/legal context could be discussed. In an interview with the IMI Programme office, project leader Hans-Georg Eichler of the European Medicines Agency (EMA), project coordinator Andre Broekmans of Lygature and deputy project leader Solange Rohou of AstraZeneca explained how the project created a change in the mindsets of players in the healthcare ecosystem, and how this will affect drug development in the future. ‘The IMI project and the nature of this multi-stakeholder collaboration was a key catalyst to accelerate a process that would otherwise have taken much, much longer to happen,’ said Eichler.
A new paper published in Nature Reviews Drug Discovery by the ADAPT SMART project highlights the progress made in discussions on Medicines Adaptive Pathways to Patients (MAPPs) through the project, as well as areas where bottlenecks remain. ###MAPPs describes the move to find ways of providing faster access to treatments for patients in urgent need, while ensuring that patients, healthcare professionals and others have sufficient information on the benefits, risks and costs of the treatment. In the paper, the authors argue that ADAPT SMART has helped to foster the evolution of an ‘adaptive mindset’, and they set out a series of ‘building blocks’ to facilitate future discussions on MAPPs. These include the need to ‘focus on speedy access for patient (sub-) populations in urgent need’; the need to use a wide range of study methods for evidence generation (including real world data), and the need to involve all stakeholders, including sponsors, patients, healthcare providers, regulators, HTA (health technology assessment) bodies and payers. The authors conclude: ‘Overall, we remain optimistic that current dynamics driven by new types of products, a more prominent patient voice and the issues of drug access and affordability will bring stakeholders together to address the challenges. We continue to believe that the building blocks of MAPPs and a shared adaptive mindset are the best option to achieving timely access for patients to transformative products in an affordable way, without compromising evidence standards.’
The IMI ADAPT SMART Closing Meeting ‘Medicines Development in the Adaptive Era’ will take place in Budapest, Hungary on 21-22 March. During the event, the final results of the project will be presented and placed into the context of public health and sustainable pharmaceutical innovation in Europe and beyond. ### As part of the programme, MIT’s NEWSDIGS (‘NEW Drug Development ParadIGmS’) programme will host an interactive session to apply the learnings from ADAPT SMART to a case study. All audience members will have the opportunity to contribute to the case study discussions. The meeting will close with a look into the future of adaptive pathways beyond ADAPT SMART. Registration is upon invitation only and seating is limited – to request an invitation, follow the link at the bottom of the event web page.
The ADAPT SMART project has issued a discussion paper on engagement criteria for MAPPs (medicines adaptive pathways to patients) to aid in debates on how and when a MAPPs approach should be used and for which medicines and diseases/conditions. The paper proposes the following set of six questions to consider when selecting individual products for a MAPPs pathway.###
- Can we define a target population with a high unmet need? Does the product hold sufficient promise to address the unmet need?
- Can a prospective iterative post- (initial) marketing authorisation development plan be proposed, developed, implemented and agreed?
- Are there workable tools to ensure appropriate product utilisation?
- Are there workable ‘strategies’ for payers in case the product under-performs?
- Is there sufficient commitment and resources from relevant stakeholders to ensure successful interactions?
- Which critical aspects for pharmaceutical development would need to be considered?
The questions are designed to initially trigger discussions at the company level (i.e. the medicine developer) and subsequently during discussions between the company and other stakeholders. These questions were designed on the basis of input gathered from a wide range of stakeholders, including regulators, payers, HTA bodies, prescribers, patients and companies. The paper is intended to inform and drive future discussions on MAPPs, both within the ADAPT SMART consortium and in the wider scientific and healthcare communities.
The question of whether, and how, patients with serious diseases should be allowed early access to promising new treatments is hotly debated. Now IMI’s ADAPT SMART project has put together a simple guide to early access that begins with the story of two fictional patients.### Jane has advanced cancer and has at best a year or two to live. John has a family history of cancer, but is currently fit and healthy. If both are told about an experimental new treatment that looks promising but needs more testing, their responses will likely be very different. John hopes that if he is diagnosed with cancer in several years’ time, the treatment will be thoroughly tested. Jane cannot wait so long, and is willing to accept the uncertainties that come with the experimental treatment. However, as the project notes, ‘healthcare decision-makers have an obligation to cater to the needs of both Jane and John’. The project goes on to explain how Medicines Adaptive Pathways to Patients (MAPPs) seek to foster access to beneficial treatments for the right patient groups at the earliest appropriate time and in a sustainable fashion. The key features of MAPPs are:
- focuses on the promise to address a high unmet need;
- provides timely access for the target population in need;
- uses an iterative development and assessment plan with evidence generation over the entire life-span of the drug;
- harnesses real world data to inform follow-on licensing and reimbursement decisions and to manage risks;
- provides for the adjustment of the treatment-eligible population;
- manages utilisation;
- facilitates the collaboration of all stakeholders (pharmaceutical companies, patients, regulators, HTAs, payers, health care providers);
- ensures the sustainability of the innovation and healthcare systems.
Information on drug development is often filled with jargon. Now IMI’s GetReal and ADAPT SMART projects have released new/updated glossaries to facilitate discussions in their respective subject areas.###
GetReal is investigating how to best incorporate ‘real world evidence’ into drug development. Its updated glossary, which was the subject of a consultation, also includes a more detailed discussion on questions such as the difference between ‘efficacy’ and ‘effectiveness’.
ADAPT SMART was set up (among other things) to coordinate IMI activities in the area of MAPPs (medicines adaptive pathways to patients). Many of the items in its glossary are drawn from the GetReal glossary. The project welcomes feedback on the glossary.
ParticipantsShow participants on map
- AbbVie Ltd, Maidenhead, United Kingdom
- Amgen, Brussels, Belgium
- Astellas Pharma Europe LTD, Chertsey, United Kingdom
- Astrazeneca AB, Södertälje, Sweden
- Bayer Pharma AG, Berlin, Germany
- Boehringer Ingelheim Internationalgmbh, Ingelheim, Germany
- Eli Lilly And Company LTD, Basingstoke, United Kingdom
- F. Hoffmann-La Roche AG, Basel, Switzerland
- Federation Europeenne D'Associations Et D'Industries Pharmaceutiques, Brussels, Belgium
- Glaxosmithkline Research And Development LTD., Brentford, Middlesex, United Kingdom
- H. Lundbeck As, Valby, Denmark
- Institut De Recherches Internationales Servier Iris, Suresnes, France
- Ipsen Innovation SAS, Les Ulis, France
- Janssen Pharmaceutica Nv, Beerse, Belgium
- Lysogene, Neuilly sur Seine, France
- Merck Kommanditgesellschaft Auf Aktien, Darmstadt, Germany
- Merck Sharp & Dohme Corp, Whitehouse Station, New Jersey, United States
- Novartis Pharma AG, Basel, Switzerland
- Novo Nordisk A/S, Bagsvaerd, Denmark
- Pfizer Limited, Sandwich, Kent , United Kingdom
- Sanofi-Aventis Recherche & Developpement, Chilly Mazarin, France
- Shire International GMBH, Zug, Switzerland
- UCB Biopharma, Brussels, Belgium
Universities, research organisations, public bodies, non-profit groups
- Haute Autorite De Sante, Saint-Denis la Plaine , France
- Massachusetts Institute Of Technology, Cambridge, United States
- National Institute For Health And Care Excellence, Manchester, United Kingdom
- The European Medicines Agency, Canary Wharf, London, United Kingdom
- University of Oxford, Oxford, United Kingdom
- Zorginstituut Nederland, Diemen, Netherlands
Small and medium-sized enterprises (SMEs) and mid-sized companies (<€500 m turnover)
- Stichting Lygature, Utrecht, Netherlands
- European Patients’ Forum (EPF), Brussels, Belgium
- Eurordis - European Organisation For Rare Diseases Association, Paris, France
Non EFPIA companies
- Agenzia Italiana Del Farmaco, Rome, Italy
|Name||IHI funding in €|
|Agenzia Italiana Del Farmaco||28 000|
|European Patients’ Forum (EPF)||78 000|
|Eurordis - European Organisation For Rare Diseases Association||78 000|
|Haute Autorite De Sante||28 000|
|National Institute For Health And Care Excellence||232 500|
|Stichting Lygature||522 000|
|University of Oxford||135 500|
|Zorginstituut Nederland||28 000|
|Total Cost||1 130 000|